TY - JOUR
T1 - Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC
T2 - Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice
AU - Le, Xiuning
AU - Sakai, Hiroshi
AU - Felip, Enriqueta
AU - Veillon, Remi
AU - Garassino, Marina Chiara
AU - Raskin, Jo
AU - Cortot, Alexis B.
AU - Viteri, Santiago
AU - Mazieres, Julien
AU - Smit, Egbert F.
AU - Thomas, Michael
AU - Iams, Wade T.
AU - Cho, Byoung Chul
AU - Kim, Hye Ryun
AU - Yang, James Chih Hsin
AU - Chen, Yuh Min
AU - Patel, Jyoti D.
AU - Bestvina, Christine M.
AU - Park, Keunchil
AU - Griesinger, Frank
AU - Johnson, Melissa
AU - Gottfried, Maya
AU - Britschgi, Christian
AU - Heymach, John
AU - Sikoglu, Elif
AU - Berghoff, Karin
AU - Schumacher, Karl Maria
AU - Bruns, Rolf
AU - Otto, Gordon
AU - Paik, Paul K.
N1 - Publisher Copyright:
2021 The Authors; Published by the American Association for Cancer Research
PY - 2022/3/15
Y1 - 2022/3/15
N2 - Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. Patients and Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity. Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (n ¼ 84) and ≥75 (n ¼ 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (n ¼ 69) versus previously treated (n ¼ 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations.
AB - Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. Patients and Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity. Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (n ¼ 84) and ≥75 (n ¼ 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (n ¼ 69) versus previously treated (n ¼ 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations.
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U2 - 10.1158/1078-0432.CCR-21-2733
DO - 10.1158/1078-0432.CCR-21-2733
M3 - Article
C2 - 34789481
AN - SCOPUS:85121458417
SN - 1078-0432
VL - 28
SP - 1117
EP - 1126
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -